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PROJECT 1: Environmental Epidemiology of Autism
EPA Grant Number: R833292C001Subproject: this is subproject number 001 , established and managed by the Center Director under grant R833292
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: UC Davis Center for Children’s Environmental Health
Center Director: Pessah, Isaac N.
Title: PROJECT 1: Environmental Epidemiology of Autism
Investigators: Hertz-Picciotti, Irva
Institution: University of California - Davis
EPA Project Officer: Fields, Nigel
Project Period: September 1, 2007 through August 31, 2011
Project Amount: Refer to main center abstract for funding details.
RFA: Centers for Children’s Environmental Health and Disease Prevention Research (2005)
Research Category: Children's Health , Health Effects
Description:
Objective:Project 1 of the UC Davis Center for Children’s Environmental Health is an epidemiological study of autism and developmental delays that will build upon our discovery of immunologic and molecular biomarkers specific to children with autism found in 2-5 year olds enrolled in the CHARGE (Childhood Autism Risks from Genetics and Environment) Study.
The hypothesis we will test is that children with autism can be distinguished from those without autism by markers of immune dysregulation (at birth, as well as post-diagnosis) and by prenatal, immunologically relevant events and exposures. The objectives are: To extend our investigation of post-diagnosis differences in genomic markers, biomarkers, and burdens of environmental chemicals of major concern among children with autism, to the pre-diagnostic period. Work in Project 1 will also examine stability over time in the immune cell markers that were determined when these children were 2-5 years old and further define molecular and cellular bases of immune cell responses to priority chemicals (PBDE, non-coplanar PCB, methyl mercury).
Approach:First, newborn blood spots from children in each of three groups (i.e., autism, developmental delay, and general population controls) will be analyzed in Project 2 for a variety of immune biomarkers and in Core 3 (Analytical Chemistry) for metal concentrations. The data obtained from newborn bloodspots, when compared to data we have already collected from the same individuals in early childhood, will provide important information for the period shortly before birth about immune dysfunction and metal exposures or metabolism in children who are later diagnosed with autism. Second, in collaboration with Core 3, we will determine if children with and without autism differ with regard to exposures, body burdens, and excretion of xenobiotics, including metals, pesticides and PBDEs. Exposures are based on questionnaire information and environmental databases covering toxic emissions, hazardous air pollutants and pesticide applications. Body burdens are measured in blood or plasma, and excretion is evaluated in hair or urine; these measurements are performed in the Core 3 laboratories. Third, we will test the hypothesis that transcriptional genomic profiles of children with autism differ from those of children without autism. Particular attention will be placed on genes related to biotic and xenobiotic metabolism. Fourth, Projects 1 and 2 in collaboration with the COTC (Core 2) will collect a second set of blood samples from 375 children who enrolled in the CHARGE study in the first project period. This study (CHARGE-BACK) will examine stability over time in the immune cell markers that were determined when these children were 2-5 years old. CHARGE-BACK blood samples will provide peripheral immune cells to study how autism alters properties of cell activation, and susceptibility to known immunotoxicants (Project 2 and Core 4). Fifth, Project 1 will launch a new cohort study that tracks 200 women at high risk of giving birth to a child who develops autism, starting from early pregnancy and following the pregnancies and the babies to the age of three years. This new cohort study is called Markers of Autism Risk in Babies – Learning Early Signs (MARBLES). Fieldwork for the MARBLES study will be tightly integrated with the COTC (Core 2) efforts, and the specimens will be evaluated in Cores 3 and 4, and in Project 2.
Expected Results:We expect to identify early predictors of autism, whether they be immunologic, genomic, or environmental.
Supplemental Keywords:autism, genes, environment, mercury, PCBs, PBDEs, immune, autoimmune, neurodevelopment, developmental neurotoxicity, persistent organic pollutants, CHARGE, MARBLES,
Main Center Abstract and Reports:
R833292
UC Davis Center for Children’s Environmental Health
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R833292C001 PROJECT 1: Environmental Epidemiology of Autism
R833292C002 PROJECT 2: Immunological Susceptibility in Autism
R833292C003 PROJECT 3: Models of Neurosusceptibility